Tissue levels of tumor necrosis factor-alpha correlates with grade of inflammation in untreated ulcerative colitis
Tissue levels of tumor necrosis factor-alpha correlates with grade of inflammation in untreated ulcerative colitis
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DOI：
10.1080/00365520701409035
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发表时间：
2007-01-01
影响因子：
1.9
通讯作者：
Florholmen, Jon
中科院分区：
文献类型：
--
作者：
Olsen, Trine;Goll, Rasmus;Florholmen, Jon
目标。溃疡性结肠炎(UC)的免疫特性一直不清楚，也存在争议。UC早期细胞因子研究之间差异的一个可能解释可能是纳入的患者正在接受免疫抑制治疗。因此，本研究的目的是测定未经治疗的UC患者肿瘤坏死因子-α(TNF-α)水平和T(H)1/T(H)2细胞因子表达(MRNA)谱。材料和方法。44名未经治疗的UC患者、10名未经治疗的克罗恩病(CD)患者和28名健康对照被纳入研究。采用实时定量聚合酶链式反应(PCR)检测结肠组织中肿瘤坏死因子-α(TNF-α)、白介素10(IL-10)、白介素18(IL-18)、白介素4(IL-4)和干扰素-γ(干扰素-γ)的基因表达。免疫组织化学(IHC)法检测T细胞(CD3)和巨噬细胞(CD68)中肿瘤坏死因子-α的表达。结果。与正常对照组比较，UC患者外周血中肿瘤坏死因子-αmRNA水平明显升高，尤以中、重度患者更为明显。UC患者肿瘤坏死因子-αmRNA水平与UC疾病活动指数(UCDAI)评分成正比。UC患者血清中干扰素-γ、IL-18、IL-4和IL-10水平与正常对照组相比也有差异。UC和CD之间只有微小的细胞因子的数量差异，而当比较中重度UC和CD时，它们或多或少是相似的。CD和UC患者固有层CD3+淋巴细胞和巨噬细胞胞内肿瘤坏死因子-α染色增强。结论。肿瘤坏死因子-α在UC中高表达，并与炎症程度相关。在CD3+淋巴细胞和巨噬细胞中均可观察到肿瘤坏死因子α的来源。中到重度UC和CD患者的细胞因子表达(MRNA)谱似乎相似。
Objective. The immune characterization of ulcerative colitis (UC) has been unclear and controversial. One possible explanation for the discrepancies between earlier cytokine studies in UC may be the fact that the patients included were on immunosuppressive therapy. Thus, the aim of this study was to determine the tumor necrosis factor-alpha (TNF-alpha) level and T(H)1/T(H)2 cytokine expression ( mRNA) profile in patients with untreated UC. Material and methods. Forty-four untreated UC patients, 10 untreated Crohn's disease ( CD) patients and 28 healthy controls were included in the study. Colon biopsies were processed for quantitative measurements of TNF-alpha, interleukin (IL)-10, IL-18, IL-4 and interferon-gamma (IFN-gamma) mRNA using real-time polymerase chain reaction (PCR). TNF-alpha expression in T-cell lymphocytes (CD3) and macrophages (CD68) were further characterized by immunohistochemistry (IHC). Results. Compared with the level in normal controls, the TNF-alpha mRNA level in UC patients was clearly increased, especially in patients with moderate to severe disease. The levels of TNF-alpha mRNA increased in proportion to the UC Disease Activity Index (UCDAI) score in UC patients. Differences were also observed between UC and controls for IFN-gamma IL-18, IL-4 and IL-10. Only minor quantitative differences in cytokines were observed between UC and CD, and they were more or less similar when comparing moderate to severe UC and CD. CD3+ lymphocytes and macrophages in lamina propria from CD and UC lesions showed increased intracellular staining of TNF-alpha. Conclusions. TNF-alpha is highly expressed in UC and correlates to the grade of inflammation. The sources of TNF-alpha were observed both in CD3+ lymphocytes and in macrophages. Cytokine expression (mRNA) profiles seem to be similar in patients with moderate to severe UC and CD.